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γ-Aminobutyric acid (GABA) neurotransmission alterations have been implicated to play a role in depression pathogenesis. While GABAA receptor positive allosteric modulators are emerging as promising in clinical practice, their precise antidepressant mechanism remains to be further elucidated. The aim of the present study was to investigate the effects of LY-02, a novel compound derived from the metabolite of timosaponin, on depression in animals and its mechanism. The results of behavioral tests showed that LY-02 exhibited better antidepressant effects in both male C57BL/6 mice and Sprague Dawley (SD) rats. The results of cellular voltage clamp experiments showed that LY-02 enhanced GABA-mediated currents in HEK293T cells expressing recombinant α6ß3δ subunit-containing GABAA receptors. Electrophysiological recording from brain slices showed that LY-02 decreased the amplitude of spontaneous inhibitory postsynaptic current (sIPSC) and increased action potentials of pyramidal neurons in the medial prefrontal cortex (mPFC) of C57BL/6 mice. Western blot results showed that LY-02 dose-dependently up-regulated the protein expression levels of brain-derived neurotrophic factor (BDNF), tropomyosin related kinase B (TrkB) and postsynaptic density protein 95 (PSD-95) in mPFC of mice. The above results suggest that LY-02, as a positive modulator of GABAA receptors, reduces inhibitory neurotransmission in pyramidal neurons. It further activates the BDNF/TrkB signaling pathway, thus exerting antidepressant effects. It suggests that LY-02 is a potential novel therapeutic agent for depression treatment.
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Antidepressivos , Fator Neurotrófico Derivado do Encéfalo , Camundongos Endogâmicos C57BL , Ratos Sprague-Dawley , Receptores de GABA-A , Animais , Masculino , Receptores de GABA-A/metabolismo , Camundongos , Antidepressivos/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Ratos , Humanos , Depressão/metabolismo , Depressão/tratamento farmacológico , Células HEK293 , Córtex Pré-Frontal/metabolismo , Receptor trkB/metabolismo , Proteína 4 Homóloga a Disks-Large/metabolismo , Células Piramidais/metabolismo , Células Piramidais/efeitos dos fármacos , Células Piramidais/fisiologiaRESUMO
BACKGROUND AND PURPOSE: Sevoflurane, a commonly used inhaled anaesthetic known for its favourable safety profile and rapid onset and offset, has not been thoroughly investigated as a potential treatment for depression. In this study, we reveal the mechanism through which sevoflurane delivers enduring antidepressant effects. EXPERIMENTAL APPROACH: To assess the antidepressant effects of sevoflurane, behavioural tests were conducted, along with in vitro and ex vivo whole-cell patch-clamp recordings, to examine the effects on GluN1-GluN2 incorporated N-methyl-d-aspartate (NMDA) receptors (NMDARs) and neuronal circuitry in the medial prefrontal cortex (mPFC). Multiple-channel electrophysiology in freely moving mice was performed to evaluate sevoflurane's effects on neuronal activity, and GluN2D knockout (grin2d-/-) mice were used to confirm the requirement of GluN2D for the antidepressant effects. KEY RESULTS: Repeated exposure to subanaesthetic doses of sevoflurane produced sustained antidepressant effects lasting up to 2 weeks. Sevoflurane preferentially inhibited GluN2C- and GluN2D-containing NMDARs, causing a reduction in interneuron activity. In contrast, sevoflurane increased action potentials (AP) firing and decreased spontaneous inhibitory postsynaptic current (sIPSC) in mPFC pyramidal neurons, demonstrating a disinhibitory effect. These effects were absent in grin2d-/- mice, and both pharmacological blockade and genetic knockout of GluN2D abolished sevoflurane's antidepressant actions, suggesting that GluN2D is essential for its antidepressant effect. CONCLUSION AND IMPLICATIONS: Sevoflurane directly targets GluN2D, leading to a specific decrease in interneuron activity and subsequent disinhibition of pyramidal neurons, which may underpin its antidepressant effects. Targeting the GluN2D subunit could hold promise as a potential therapeutic strategy for treating depression.
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Antidepressivos , Interneurônios , Camundongos Endogâmicos C57BL , Camundongos Knockout , Córtex Pré-Frontal , Receptores de N-Metil-D-Aspartato , Sevoflurano , Animais , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/metabolismo , Sevoflurano/farmacologia , Antidepressivos/farmacologia , Interneurônios/efeitos dos fármacos , Interneurônios/metabolismo , Masculino , Camundongos , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Éteres Metílicos/farmacologia , Potenciais de Ação/efeitos dos fármacos , Depressão/tratamento farmacológico , Anestésicos Inalatórios/farmacologiaRESUMO
BACKGROUND: Postpartum depression (PPD) is a serious psychiatric disorder that has significantly adverse impacts on maternal health. Metabolic abnormalities in the brain are associated with numerous neurological disorders, yet the specific metabolic signaling pathways and brain regions involved in PPD remain unelucidated. METHODS: We performed behavioral test in the virgin and postpartum mice. We used mass spectrometry imaging (MSI) and targeted metabolomics analyses to investigate the metabolic alternation in the brain of GABAAR Delta-subunit-deficient (Gabrd-/-) postpartum mice, a specific preclinical animal model of PPD. Next, we performed mechanism studies including qPCR, Western blot, immunofluorescence staining, electron microscopy and primary astrocyte culture. In the specific knockdown and rescue experiments, we injected the adeno-associated virus into the central amygdala (CeA) of female mice. RESULTS: We identified that prostaglandin D2 (PGD2) downregulation in the CeA was the most outstanding alternation in PPD, and then validated that lipocalin-type prostaglandin D synthase (L-PGDS)/PGD2 downregulation plays a causal role in depressive behaviors derived from PPD in both wild-type and Gabrd-/- mice. Furthermore, we verified that L-PGDS/PGD2 signaling dysfunction-induced astrocytes atrophy is mediated by Src phosphorylation both in vitro and in vivo. LIMITATIONS: L-PGDS/PGD2 signaling dysfunction may be only responsible for the depressive behavior rather than maternal behaviors in the PPD, and it remains to be seen whether this mechanism is applicable to all depression types. CONCLUSION: Our study identified abnormalities in the L-PGDS/PGD2 signaling in the CeA, which inhibited Src phosphorylation and induced astrocyte atrophy, ultimately resulting in the development of PPD in mice.
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Astrócitos , Atrofia , Depressão Pós-Parto , Modelos Animais de Doenças , Prostaglandina D2 , Transdução de Sinais , Animais , Astrócitos/patologia , Astrócitos/metabolismo , Feminino , Depressão Pós-Parto/patologia , Depressão Pós-Parto/metabolismo , Camundongos , Transdução de Sinais/fisiologia , Prostaglandina D2/metabolismo , Núcleo Central da Amígdala/metabolismo , Oxirredutases Intramoleculares/genética , Oxirredutases Intramoleculares/metabolismo , Lipocalinas/genética , Lipocalinas/metabolismo , Quinases da Família src/metabolismo , Camundongos KnockoutRESUMO
OBJECTIVE: To explore the effects of Draf1-3 on frontal sinus airflow and frontal sinus irrigation in people with different frontal sinus development METHODS: The development of the frontal sinus and the distribution of the frontal recess cells were evaluated by CT scan in 150 adults (300 sides). The airflow changes into the frontal sinus and frontal recess after Draf were analyzed by Fluent software under a steady state and quiet inspiratory state. Nasal irrigation after Draf in adults with well-developed frontal sinus was simulated using 120 mL saline at a rate of 12 mL/s in a position at 45° to observe the changes in transient flow distribution. RESULTS: The moderately developed type of the frontal sinus was the most common. The airflow patterns in the frontal sinus and frontal recess in the moderate development group were laminar, while several large vortexes were formed between the frontal sinus and frontal recess in the well-development group. The Draf exerted more significant effects on the patterns, pressure, and velocity of the airflow in the frontal sinus and frontal recess in the well development group than in the moderate development group. The volume fraction of saline in the frontal sinus increased significantly from Draf1 to Draf3, and the time required for a complete infiltration of saline in the frontal sinus mucosa was significantly reduced. CONCLUSIONS: Draf1-3 has different effects on the airflow field of the frontal sinus with different developmental types; and Draf1-3 can significantly improve the postoperative flushing of the frontal sinus.
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Seio Frontal , Adulto , Humanos , Seio Frontal/diagnóstico por imagem , Seio Frontal/cirurgia , Hidrodinâmica , Simulação por Computador , Tomografia Computadorizada por Raios X , Lavagem Nasal , EndoscopiaRESUMO
Objective:To investigate the efficacy of functional endoscopic sinus surgeryï¼FESSï¼ in the treatment of olfactory dysfunction in patients with chronic rhinosinusitis with nasal polyps ï¼CRSwNPï¼ , at the same time, it provides an evidence for the prognosis evaluation of olfaction and the clinical application of oERPs to evaluate the plasticity of olfaction cortex. Methods:From October 2021 to October 2022, 45 patients with CRSwNP who underwent FESS nine-step standardized treatment in our department were recruited as the research subjects, divided into 22 patients with eosinophilic CRSwNPï¼ECRSï¼and 23 patients with non-eosinophilic CRSwNPï¼nECRSï¼. VAS-olfactory dysfunction ï¼VAS-ODï¼ score, SNOT-22 olfactory score, Sniffin' Sticks test and oERPs collection and processing were performed before the operation. All items were evaluated again 3 months after the operation. Results:VAS-OD and SNOT-22 olfactory score were significantly lower in all CRSwNP patients after the operation than those before the operation[Fï¼1, 43ï¼ =357.429, P<0.001; Fï¼1, 43ï¼ =185.657, P<0.001], the scores of T, D, I and TDI scores in Sniffin' Sticks test were significantly higher than those before the operation[Fï¼1, 43ï¼ =126.302, P<0.001; Fï¼1, 43ï¼ =311.301, P<0.001; Fï¼1, 43ï¼ =131.401, P<0.001; Fï¼1, 43ï¼ =295.885, P<0.001]; The decrease of VAS-OD and SNOT-22 olfactory score in the ECRS group was smaller than that in the nECRS group[Fï¼1, 43ï¼ =4.825, P=0.033; Fï¼1, 43ï¼ =9.916, P=0.003], T, D and TDI scores were significantly lower in nECRS group than those in nECRS group[Fï¼1, 43ï¼ =6.719, P=0.013; Fï¼1, 43ï¼ =4.890, P=0.032; Fï¼1, 43ï¼ =4.469, P=0.040]; There was a positive correlation between preoperative eosinophil-to-lymphocyte ratioï¼ELRï¼ and SNOT-22 olfactory score and how much it changesï¼r=0.455, P=0.002; r=-0.414, P=0.005ï¼, a negative correlation between T, TDI score and how much they change respectivelyï¼r=-0.431, P=0.003; r=-0.385, P=0.009; r=-0.383, P=0.010; r=-0.316, P=0.035ï¼. The latency of P3 was significantly shorter after operation than that before operation in all CRSwNP patients[Fï¼1, 14ï¼ =24.840, P<0.001], however, the amplitude has no significant surgical effect. Conclusion:FESS could significantly improve the olfactory function of CRSwNP patients, while changes in plasticity may occur in the olfactory cortex. In addition, the preoperative peripheral blood eosinophil granulocyte level can predict the postoperative olfactory improvement.
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Pólipos Nasais , Transtornos do Olfato , Rinite , Sinusite , Humanos , Estudos Prospectivos , Pólipos Nasais/complicações , Pólipos Nasais/cirurgia , Rinite/complicações , Rinite/cirurgia , Sinusite/complicações , Sinusite/cirurgia , Transtornos do Olfato/etiologia , Doença Crônica , Endoscopia/efeitos adversosRESUMO
AIMS: Anxiety disorders associated with pain are a common health problem. However, the underlying mechanisms remain poorly understood. We aimed to investigate the role of paraventricular nucleus (PVN)-central nucleus of the amygdala (CeA) oxytocinergic projections in anxiety-like behaviors induced by inflammatory pain. METHODS: After inflammatory pain induction by complete Freund's adjuvant (CFA), mice underwent elevated plus maze, light-dark transition test, and marble burying test to examine the anxiety-like behaviors. Chemogenetic, optogenetic, and fiber photometry recordings were used to modulate and record the activity of the oxytocinergic projections of the PVN-CeA. RESULTS: The key results are as follows: inflammatory pain-induced anxiety-like behaviors in mice accompanied by decreased activity of PVN oxytocin neurons. Chemogenetic activation of PVN oxytocin neurons prevented pain-related anxiety-like behaviors, whereas inhibition of PVN oxytocin neurons induced anxiety-like behaviors in naïve mice. PVN oxytocin neurons projected directly to the CeA, and microinjection of oxytocin into the CeA blocked anxiety-like behaviors. Inflammatory pain also decreased the activity of CeA neurons, and optogenetic activation of PVNoxytocin -CeA circuit prevented anxiety-like behavior in response to inflammatory pain. CONCLUSION: The results of our study suggest that oxytocin has anti-anxiety effects and provide novel insights into the role of PVNoxytocin -CeA projections in the regulation of anxiety-like behaviors induced by inflammatory pain.
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Núcleo Central da Amígdala , Ratos , Camundongos , Animais , Núcleo Hipotalâmico Paraventricular , Ocitocina , Ratos Wistar , Ansiedade/etiologia , Transtornos de Ansiedade , DorRESUMO
Calcium channel blockers and magnesium sulfate are frequently used together, particularly in women with underlying chronic hypertension and pre-eclampsia. A review of the literature showed prolonged neuromuscular blockade after treatment with magnesium sulfate. Since magnesium and calcium have opposite effects on the neuromuscular junctions, muscle weakness may become a postoperative manifestation of magnesium sulfate and calcium antagonist treatment in the obstetric population; however, limited information is available regarding this postulation. Here, we report a case wherein rocuronium activity was markedly prolonged due to pretreatment with magnesium sulfate and nicardipine after general anesthesia during an emergency cesarean delivery.
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Studies have shown that phosphatase and tensin homolog deleted on chromosome ten (PTEN) participates in the regulation of cochlear hair cell survival. Bisperoxovanadium protects against neurodegeneration by inhibiting PTEN expression. However, whether bisperoxovanadium can protect against noise-induced hearing loss and the underlying mechanism remains unclear. In this study, we established a mouse model of noise-induced hearing loss by exposure to 105 dB sound for 2 hours. We found that PTEN expression was increased in the organ of Corti, including outer hair cells, inner hair cells, and lateral wall tissues. Intraperitoneal administration of bisperoxovanadium decreased the auditory threshold and the loss of cochlear hair cells and inner hair cell ribbons. In addition, noise exposure decreased p-PI3K and p-Akt levels. Bisperoxovanadium preconditioning or PTEN knockdown upregulated the activity of PI3K-Akt. Bisperoxovanadium also prevented H2O2-induced hair cell death by reducing mitochondrial reactive oxygen species generation in cochlear explants. These findings suggest that bisperoxovanadium reduces noise-induced hearing injury and reduces cochlear hair cell loss.
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AIMS: We compared analgesic outcomes between single-orifice and multiorifice wire-reinforced catheters under 480 mL/hour delivery rate with programmed intermittent epidural bolus administration. METHODS: Between August and November 2021, 182 nulliparous and healthy women with singleton pregnancy, 2-5 cm cervical dilation, and requesting neuraxial analgesia were randomized to receive either single-orifice or multiorifice catheters. Epidural analgesia was initiated and maintained with 0.1% ropivacaine and 0.3 µg/mL sufentanil. Programmed intermittent epidural bolus volume of 10 mL was administered every 45 min at 480 mL/hour beginning immediately after the test dose. Primary outcome was the percentage of parturients in the two groups with adequate analgesia 20 min after the initial bolus. RESULTS: Compared with multiorifice catheters, single-orifice catheters were associated with a higher proportion of parturients with adequate analgesia (71.8% vs 56.0%, respectively; 95% CI 1.3% to 29%, p=0.03) and more frequent S2 sensory blockade (37.6% vs 22.6%, respectively; 95% CI -30% to 1%, p=0.03) 20 min after block initiation. Median time (IQR) to adequate analgesia was 12 (8-30) min and 20 (10-47) min with single-orifice and multiorifice catheters, respectively (95% CI 0.1 to 0.7 min, p<0.01). The median (IQR) ropivacaine consumption per hour was higher in parturients receiving multiorifice catheters than those with single-orifice catheters (15.3 (13.3-17.0) mg/hour vs 13.3 (13.3-15.4) mg/hour, respectively; 95% CI 0.2 to 0.8 mg/hour, p<0.001). CONCLUSION: Single-orifice catheters used for programmed intermittent epidural bolus at 480 mL/hour for epidural labor analgesia had improved analgesic efficacy than multiorifice catheters. TRIAL REGISTRATION NUMBER: ChiCTR2100049872.
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Analgesia Epidural , Analgesia Obstétrica , Gravidez , Feminino , Humanos , Ropivacaina , Anestésicos Locais , Analgésicos , Catéteres , DorRESUMO
Introduction: This study aimed to explore the personal and organizational factors influencing the lack of implementation of epidural labor analgesia (ELA). Methods: This study was conducted at the Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China. A total of 451 women who underwent vaginal delivery without ELA between 8 October 2021 and 30 March 2022, were included. A questionnaire was used to collect the relevant data. We derived and validated the variable, without ELA, by using binary logistic regression analysis. Results: Of the total 451 included, 355 (78.7%) initially preferred ELA, whereas 96 (21.3%) rejected it directly. Five variables were validated (p < 0.05): multiparas, ELA would lead to back pain, experienced ELA in previous delivery, the inner attitude toward labor pain, and blood routine and coagulation function not being tested within 14 days. The sensitivity and specificity of this model were 96.3 and 69.8%, respectively. Conclusion: The corresponding training should be provided to the medical staff to identify women at high risk of rejecting ELA during the prenatal examination process using a questionnaire, then provide them with knowledge regarding ELA, so that ELA can benefit more mothers. Additionally, the existing organizational factor should be addressed in order to efficiently provide ELA services to mothers. Clinical trial registration: This study was registered at the Chinese Clinical Trial Registry (Chi CTR 2000034625) on July 12, 2020.
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Esophageal cancer is a highly aggressive and lethal human malignancy. The current study was established with the aim of studying the role of the lncRNA NEAT1 in regulating the growth and progression of esophageal cancer. Esophageal cancer tissues and cell lines showed significantly (P<0.05) upregulated transcript levels of lncRNA NEAT1. The expression of NEAT1 was also upregulated in metastatic tissues compared to nonmetastatic. The elimination of lncRNA NEAT1 led to a significant decrease (P<0.05) decrease in the viabilities of cancer cells due to the induction of apoptosis. Cancer cell migration and invasion were also significantly reduced (P<0.05) upon lncRNA NEAT1. In silico analysis indicated that miR-377 targets lncRNA NEAT1 at the post-transcriptional level, whose overexpression in cancer cells was found to mimic the tumor-suppressive regulatory effects of lncRNA-NEAT1. At the molecular level, the regulatory effects of lncRNA NEAT1 were shown to be modulated by the miR-377/E2F3 signaling axis. The results suggest that the molecular targeting of the lncRNA NEAT1 and miR-377/E2F3 axis could prove beneficial in the management of esophageal cancer.
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Fator de Transcrição E2F3 , Neoplasias Esofágicas , MicroRNAs , RNA Longo não Codificante , Humanos , Linhagem Celular Tumoral , Proliferação de Células/genética , Fator de Transcrição E2F3/genética , Fator de Transcrição E2F3/metabolismo , Neoplasias Esofágicas/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismoRESUMO
Pregnancy and childbirth are major life events for women and their families, characterized by physical, psychological, and emotional changes that can trigger anxiety, depression, and mental disorders in susceptible individuals. Acute labor pain is an independent risk factor for persistent pain in the postpartum period and is associated with depressive disorders. Epidural analgesia is a well-established technique that has commonly been regarded as the gold standard in pain management during labor. Although the relationships between labor pain, labor epidural analgesia, and postpartum depression have been studied by many investigators, the results of these studies are conflicting. Some literature suggest that labor epidural analgesia is associated with a reduction in the incidence of postpartum depression; however, other studies have failed to demonstrate this association. Unmet analgesic needs expectations, unmet birth expectations, and/or the quality of social support during labor may contribute to postpartum depression. The limitations of the published studies included differential misclassification of study variables and residual confounding, variations in the diagnosis of depression, and incomplete history data. Thus, future studies should include information on sociodemographic and patient-level variables and assessments of pain during labor or in the postpartum period. Better management of labor pain should be provided to prevent long-term morbidity and improve maternal and neonatal outcomes. Anesthesiologists could collaboratively work with obstetricians and perinatal psychiatrists to ensure that hospitals prioritize screening and treatment for postpartum depression.
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Objective:According to the characteristics of endoscopic transnasal and transoral surgery for infratemporal fossa tumors, we divided and named subzones of the infratemporal fossa, to explore the approaches of endoscopic transnasal and transoral surgery for infratemporal fossa tumors, and to analyze their advantages and disadvantages. Methods:We retrospectively analyzed the clinical data of 36 patients with benign tumors of infratemporal fossa successfully resected through nose or mouth under endoscope, summarized and analyzed the localization characteristics of these tumors in infratemporal fossa, and made a subzone naming rule of infratemporal fossa. We also summarized the selection principles, advantages and disadvantages of endoscopic transnasal and transoral surgical approaches. Results:The infratemporal fossa area is divided into ABC area. Area A is the fat pad area posterolateral of maxillary sinus. Area B is further divided into B1 ï¼above the plane of maxillary sinus floor, anterior styloid processï¼, B2 ï¼below the plane of maxillary sinus floor, anterior styloid processï¼, and B3 ï¼posterior styloid process to anterior vertebraï¼; Area C is retropharyngeal and eustachian tube area. The location of the tumor in the infratemporal fossa determines the choice of transnasal and transoral approaches. All tumors were completely removed, and no tumor recurred during the follow-up. A few patients had temporary local sensory function decline, and recovered during the follow-up. Conclusion:The infratemporal fossa region naming rule according to the characteristics of endoscopic transoral and transnasal surgery approach is simple and practical, which can effectively guide the operation of the infratemporal fossa region and has clinical application value.
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Fossa Infratemporal , Procedimentos Cirúrgicos Bucais , Levantamento do Assoalho do Seio Maxilar , Endoscopia , Humanos , Seio Maxilar , Recidiva Local de Neoplasia , Estudos RetrospectivosRESUMO
The sense of smell is one of the five most primitive human sensory functions, and it plays a very important role in our daily lives. Despite numerous methods for evaluating olfactory function, there is still a lack of standardization of olfactory tests and the results are often inconsistent. Furthermore, the related research on objective evaluation started relatively late. Along with the deciphering of the olfactory pathway, the technical level of olfactory objective inspection has been greatly improved and significant progress has also been made in terms of clinical application, such as: olfactory pathway MRI and fMRI imaging, OERPs, BEAM for various olfactory disorders and early diagnosis of neurodegenerative disorders, as well as related research based on bionic olfactory sensing technology. This article mainly introduces the recent research progress of several commonly used objective olfactory tests and provides reference for more accurate evaluation of olfactory function.
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Transtornos do Olfato , Humanos , Imageamento por Ressonância Magnética , Transtornos do Olfato/diagnóstico , Condutos Olfatórios , Pesquisa , OlfatoRESUMO
OBJECTIVE: This study aimed to examine the olfactory and gustatory dysfunctions (OGDs) among hospitalized patients with a novel strain of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), lineage B.1.617.2, also known as the delta variant, in Xi'an, China through verbal interviews. METHODS: Clinical information of 370 hospitalized patients infected with the delta variant in the Aerospace City Branch of Xi'an People's Hospital in Xi'an, China from December 27, 2021 to January 10, 2022 were collected. The prevalence and characteristics of OGDs were collected using a simple questionnaire submitted to all infected patients, including questions about the presence and absence of OGDs. RESULTS: Among the 370 patients infected with the delta variant, 28 (7.6%) reported OGDs. A significant proportion of patients with self-reported OGDs were younger than those without (28.9 ± 10.5 vs. 35.3 ± 13.9, P = 0.005) and had significantly higher rates of sore throat and rhinitis (28.6% vs. 12.3%, P = 0.033; 42.9% vs. 9.9%, P = 0.000). Women were significantly more affected by OGDs than men (67.9% vs. 32.1%, P = 0.012). Vaccinated and unvaccinated delta variant-infected patients showed statistically significant differences in terms of disease severity (P = 0.002). CONCLUSIONS: The prevalence of OGDs in the delta variant infection was lower than that in wild-type SARS-CoV-2 infection. Meanwhile, young age, female sex, and upper respiratory tract symptoms could be closely related to the occurrence of OGDs in the delta variant infection. In addition, a satisfactory level of efficacy was obtained with coronavirus disease 2019 vaccines against moderate and severe delta variant infections.
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OBJECTIVE: The combination of dural puncture epidural (DPE) technique and programmed intermittent epidural bolus (PIEB) is a novel alternative labor analgesia regimen providing rapid analgesia onset and improved analgesia quality. However, the optimum PIEB settings for using the DPE technique remain unclear. DESIGN: Biased-coin up-and-down sequential allocation design. SETTING: Labor analgesia. PATIENTS: Forty nulliparous women requesting labor analgesia. INTERVENTIONS: Dural was punctured using a 25-gauge Whitacre needle. 12 mL of 0.1% ropivacaine with 0.3 µg/mL of sufentanil was used for initiation. Labor analgesia was maintained using the same solution with a fixed 8 mL volume beginning 1 h after initiation. The interval for the first patient was 60 min and varied for subsequent patients according to the biased-coin design (groups 60, 50, 40, and 30; interval 60, 50, 40, and 30 min, respectively). MEASUREMENTS: The primary outcome was adequate analgesia, defined as no request of patient-controlled epidural analgesia or provider boluses for 6 h after the epidural analgesia initiation or until the maternal cervix was fully dilated, whichever came first. The secondary outcomes included sensory blockade level, motor strength, maternal hypotension, and pruritus. RESULTS: The estimated effective interval in 90% of participants was 41.5 min (95% CI 39.5-43.5 min) and 40.5 min (95% CI 33.7-47.5 min) by the truncated Dixon and Mood method and the isotonic regression method, respectively, for the 40 women included. The proportions of patients with the highest sensory block level achieving or above T6 were 60%, 26%, 27%, and 0% in groups 30, 40, 50, and 60, respectively. One patient presented a Bromage score of 1. There was a low incidence of hypotension in all the groups with no need for vasopressor treatment. CONCLUSIONS: The optimum PIEB interval time between 8 mL boluses of ropivacaine 0.1% and sufentanil 0.3 µg/mL when using the DPE technique was approximately 41 min.
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Analgesia Epidural , Analgesia Obstétrica , Hipotensão , Analgesia Epidural/efeitos adversos , Analgesia Epidural/métodos , Analgesia Obstétrica/efeitos adversos , Analgesia Obstétrica/métodos , Analgésicos , Anestésicos Locais , Método Duplo-Cego , Feminino , Humanos , Masculino , Punções , Ropivacaina , Sufentanil/efeitos adversosRESUMO
Background: Norepinephrine has been associated with improved heart rate (HR) and cardiac output (CO) compared to phenylephrine as a treatment for post-spinal hypotension during caesarean delivery (CD) in singleton pregnancies. Our current study compared the effects of norepinephrine and phenylephrine in maintaining maternal hemodynamics after spinal anaesthesia in twin pregnancies during elective CD. Methods: This was a double-blinded, randomized, controlled study. From December 2017 to December 2018, 62 women with healthy twin term pregnancies undergoing elective CD under spinal anaesthesia were studied. Following spinal induction, either norepinephrine (6 µg/mL) or phenylepinephrine (75 µg/mL) was infused at 60 mL/h to maintain systolic blood pressure (SBP) near baseline until delivery. HR, SBP, systemic vascular resistance (SVR), and CO were collected using anaesthesia monitors and continuous-pulse waveform analysis. The primary outcome was maternal CO. Other parameters of maternal hemodynamics, umbilical cord blood gases, and adverse events were also compared. Results: Hemodynamic variables (CO, SBP, HR, and SVR) between spinal anaesthesia induction to skin incision were similar between the two groups (P = 0.889, 0.057, 0.977, and 0.416, respectively). The incidence of bradycardia was significantly higher in the phenylephrine group (69%) than in the norepinephrine group (24.2%, P<0.001). Maternal nausea and vomiting, hypotension, reactive hypertension, and neonatal outcomes did not differ between the groups. Conclusion: When administered as a prophylactic fixed-rate infusion, phenylephrine and norepinephrine are both capable of maintaining maternal blood pressure following spinal anaesthesia in twin pregnancies. There were no differences in the maternal hemodynamics or foetal outcomes between women receiving norepinephrine and phenylephrine. Previous Presentations: Presented at the 51st Society for Obstetric Anesthesia and Perinatology Annual Meeting, Phoenix, Arizona, May 1-5, 2019. Clinical Trial Number and Registry: No. ChiCTR-IOR-17013358.